title: Neuropeptide Y as a stimulator of Na+ -dependent Ca2+ efflux from freshly isolated adult rat cardiomyocytes.
abstract: Several physiological stimuli cause a rise in intracellular Ca2+ concentration ([Ca2+]i) in cardiomyocytes. This increased [Ca2+]i must be restored to physiological resting level to ensure response to further stimuli. In the present study, we examined the effect of neuropeptide Y (NPY), which is secreted from certain adrenergic or nonadrenergic neurons, on Ca2+ efflux from freshly isolated, quiescent adult rat cardiomyocytes. The isolated cardiomyocytes were preloaded with 45CaCl2 for 1 h. Then, the fractional release of 45Ca2+ from the cells was measured. NPY stimulated the efflux of 45Ca2+ from isolated adult rat cardiomyocytes in a concentration-dependent manner (10(-8) M to 10(-6) M). NPY (10(-6) M)-induced Ca2+ efflux was 2.0 +/- 0.16% of the total cellular content. The 45Ca2+ efflux from the cells was also stimulated by Y1 receptor agonist, [Leu31, Pro34]NPY, but not by Y2 receptor agonist, NPY13-36. The effect of NPY was inhibited by a peptide NPY inhibitor, NPY18-36 and a non-peptide NPY inhibitor, benextramine to a similar extent. From these results, it is conceivable that the effect of NPY on Ca2+ efflux from cardiomyocytes is mediated through Y1 receptors. It was also observed that NPY caused a rise in [Ca2+]i to almost 150 nM. NPY-stimulated 45Ca2+ efflux was not affected by removal of extracellular Ca2+, but was dependent on the presence of extracellular Na+. Moreover, NPY caused a 22Na+ influx into the cells of about 1.6-fold over the basal value which was inhibited by amiloride and 5-(N,N-dimethyl)-amiloride, known Na+/Ca2+ exchange inhibitors. In addition, isoproterenol also caused 45Ca2+ efflux from the cells and which was enhanced by the addition of NPY. These results suggest that NPY stimulates extracellular Na+-dependent 45Ca2+ efflux from freshly isolated adult rat cardiomyocytes, probably through its stimulatory effect on plasma membrane Y1 receptors with which NPY may couple during Na+/Ca2+ exchange.
authors.affiliation: Department of Cardiovascular Surgery, School of Medicine, The University of Tokushima, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Horike
authors.forename: M
authors.initials: M
authors.lastname: Yoshizumi
authors.forename: T
authors.initials: T
authors.lastname: Kitagawa
authors.forename: K
authors.initials: K
authors.lastname: Itoh
authors.forename: H
authors.initials: H
authors.lastname: Houchi
authors.forename: T
authors.initials: T
authors.lastname: Tamaki
authors.forename: I
authors.initials: I
authors.lastname: Katoh
mesh_terms: D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003538:Cystamine / Q000031:analogs & derivatives / Q000494:pharmacology; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009478:Neuropeptide Y / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000494:pharmacology*
chemical_list: D009478:Neuropeptide Y; C029998:benextramine; D012964:Sodium; D000251:Adenosine Triphosphatases; C034688:sodium calcium ATPase; D003538:Cystamine; D002118:Calcium